Understanding the ameliorative effects of green tea catechins on glycation:A structure-activity correlation study

Chronic hyperglycemia in diabetes mellitus leads to non-enzymatic protein glycation and the formation of advanced glycation end-products (AGEs), driving diabetic complications. Natural polyphenols, such as tea catechins, are promising therapeutic agents to mitigate this process. This study provides a comprehensive in vitro evaluation of four major tea catechins - (+)-Catechin (C), (-)-Epicatechin (EC), (-)-Epigallocatechin (EGC), and (-)-Epigallocatechin gallate (EGCG) for their anti-glycation potential, aiming to establish a structure-activity relationship (SAR). The inhibitory effects of catechins were assessed using a Bovine Serum Albumin (BSA)-glucose glycation model. Spectroscopic techniques, such as UV-Visible spectroscopy, Circular Dichroism, and intrinsic fluorescence spectroscopy, were employed to assess structural changes in proteins induced by glycation. Thioflavin T and Congo Red assays were used to determine if glycation also leads to aggregation. The Nitroblue Tetrazolium assay was used to detect early-stage Amadori product formation. FRAP, DPPH and ABTS assays were used to monitor the antioxidant capacity of catechins. Molecular docking simulations were also used to analyze the potential interaction between catechins and BSA.The antiglycation potential of catechins was in the order of EGCG > EGC > Epicatechin > Catechin and this order was consistent across all parametric tests. EGCG was the most potent inhibitor, reducing Amadori product formation by 88.0%, preserving α-helical content and demonstrating the highest antioxidant capacity in enzyme inhibition assays. Molecular docking revealed that EGCG had the strongest binding affinity to BSA (-8.3 kcal/mol), which correlated with its better activity.